Gastrointestinal cancer refractory to chemotherapy: a role for octreotide?

Although octreotide has been shown to inhibit the growth of gastrointestinal (GI) tumors in vitro and in vivo, preliminary clinical trials have reported disappointing results for this somatostatin analog in patients with GI cancers. The results of these trials probably reflect the difficulty in assessing the therapeutic potential of an agent such as octreotide in GI cancers. Thus, it is possible that treatment with octreotide could be useful in the stabilization of disease if it is associated with an improvement in survival. On the basis of these considerations five randomized trials were carried out to evaluate the therapeutic potential in patients with GI cancers. Four trials (one in patients with colorectal carcinoma and three in patients with carcinoma of the pancreas) did not show any advantage of octreotide in untreated patients; in contrast, one trial reported that octreotide prolonged survival in patients with GI cancers refractory to chemotherapy. Some clinical features of the latter study (treatment with chemotherapy, different schedules) may explain these conflicting results. Although data from randomized trials suggest that octreotide is not effective in untreated asymptomatic advanced GI cancer patients, further studies are warranted to assess the efficacy of octreotide in chemotherapy refractory patients in order to clarify the impact of octreotide in terms of not only survival but also on the patients' quality of life.     

Spiral CT for lung cancer screening: is it ready for prime time?

Low-dose spiral computed tomography (CT) shows promise as a screening test for lung cancer, as it detects many more malignant pulmonary nodules than does standard plain radiography of the chest. Yet until more data are available we need to temper our enthusiasm. No studies have yet determined if using low-dose spiral CT as a screening test will lead to lower mortality rates. This paper reviews the issue of lung cancer screening and low-dose spiral CT.     

Controversial issues: a case for neutrality?

Controversial issues are defined, in this discussion, as those in relation to which contrary views can be held without those views being contrary to reason. Such issues arise in the range of courses constituting nurse education, especially, but not exclusively, where ethical questions are discussed. The nurse educator may, therefore, have to decide whether or not to say what she thinks, in particular she may have to decide whether or not to assert her own view as correct. Where professional beliefs and values are involved, to assert a view as correct may seem to be required. Might this, though, detract from the aim of developing students' capacity for autonomous reflection? The discussion assesses whether neutrality, in the sense either of not stating one's view or not asserting it as correct, is desirable, by examining arguments both for and against, and highlights ways in which a neutral stance both is, and is not, an option.     

Lung cancer screening: is it time for a change in policy?

Two recent studies of computed tomography (CT) as a screening test for lung cancer have heightened debate about this topic. Although the International Early Lung Cancer Action Program investigators (N Engl J Med 2006; 355:1763-1771) concluded that annual CT screening can detect lung cancer that is curable, Bach et al (JAMA 2007; 297:953-961) concluded that it may not meaningfully reduce the risk of advanced lung cancer or death from lung cancer. We feel that questions remain about the degree of reduction in lung cancer-specific mortality, the potential morbidity caused by screening, the appropriate group to screen, and the cost-effectiveness of screening. These questions warrant further study prior to accepting CT screening as the standard of care. Hopefully, much of this knowledge will be gained when the results of ongoing controlled studies are available.     

Is there a role for screening asymptomatic patients with diabetes?

Coronary artery disease (CAD) remains a leading cause of death among patients with diabetes mellitus. However, many patients with diabetes and CAD are asymptomatic and may sustain a myocardial infarction as their presenting symptom of CAD. Non-invasive cardiovascular imaging offers an opportunity to detect the presence and severity of CAD, or its hemodynamic consequences. The Detection of Ischemia in Asymptomatic Diabetics study and the FACTOR-64 study examined the utility of non-invasive imaging tests to evaluate asymptomatic individuals with diabetes mellitus. The results of these trials may have been negative with regard to promoting CAD screening of asymptomatic diabetic patients, but they do strengthen the position of optimal medical management in reducing cardiovascular events. However, performing a trial to include true high-risk patients who have CAD and are more likely to have silent ischemia could lead to prognostically beneficial coronary revascularizations.     

Whole-body CT screening for cancer and coronary disease: does it pass the test?

Even though whole-body CT scanning is being marketed directly to patients and they are starting to demand it, does it meet the standards of a good screening test for cancer and coronary artery disease? This article is a step-by-step, disease-specific discussion of the characteristics of a good screening test, and whether whole-body CT scanning meets these standards.     

Management of breast cancer: is there a role for somatostatin and its analogs?

Somatostatin and related peptides are a family of peptides which are ubiquitous and function as endogenous growth inhibitors. Analogs have been developed through the introduction of a D-amino acid in the position 8 of somatostatin moiety which is more resistant to the action of endogenous peptidases than the parental moiety. Both somatostatin and its analogs interact with specific receptors on the cell surface. The five receptor subtypes, SSTR-1 to SSTR-5, which have been characterized so far, have a different affinity for somatostatin and its analogs. This and the fact that receptors are not homogeneously expressed in tissues account for the different activity of these compounds, all of which have demonstrated tumoristatic properties both in vitro and in vivo. The interaction of somatostatin and of somatostatin analogs with specific SSTR receptors is crucial to the antiproliferative mechanisms exerted by these compounds in vitro and in some animal models and the various pathways have been reviewed in detail. However, inhibition of angiogenesis and suppression of lactogenic hormones might represent alternative mechanisms, in particular in breast cancer. The rationale for the use of somatostatin and its analogs in breast cancer patients and to combine these peptides with antihormones, like antiestrogens or prolactin-lowering drugs, or cytotoxics has been reviewed together with the results obtained in phase II and comparative trials. The reasons for the limited efficacy shown by these compounds either when used alone or when used in combination with other drugs have also been critically reviewed in the perspective of new trials.     

Dehydroepiandrosterone: is there a role for replacement?

Dehydroepiandrosterone (DHEA) and its sulfated ester are found in high concentrations in the plasma; however, their role in normal human physiology, other than as precursors for sex hormones, remains incompletely defined. Studies of rodent models have shown that these hormones have beneficial effects on a wide variety of conditions, such as diabetes, obesity, immune function, atherosclerosis, and many of the disorders associated with normal aging. However, rodents are not the best models to study the actions of these hormones because they have very little endogenous DHEA; thus, the doses given to these animals are usually suprapharmacological. Human studies have been performed to determine the potential beneficial effects of DHEA replacement in persons with low DHEA levels. Results have been conflicting. Human studies suggest a potential role for DHEA replacement in persons who have undergone adrenalectomy and possibly in the aging population. However, long-term studies assessing the benefits vs adverse effects must be done before DHEA replacement can be recommended.     

Pro-healing drug-eluting stents: a role for antioxidants?

Current strategies to lower the incidence of ISR (in-stent restenosis) following PCI (percutaneous coronary intervention) are aimed at modifying arterial healing after stent injury. This can impair endothelial recovery and render the vessel prone to acute thrombosis. As early restoration of endothelial integrity inhibits neointimal growth and thrombosis, alternative approaches which encourage this process may provide a more effective long-term result after PCI. Oxidative stress is enhanced after PCI and participates in the regulation of endothelial regeneration and neointimal growth. Moreover, evidence suggests antioxidants improve re-endothelialization and inhibit ISR. By promoting, rather than blocking, the healing process, antioxidant and other therapies may offer an alternative or additional approach over the antiproliferative approaches common to many current devices.